Drug repurposing to overcome resistance to various therapies for colorectal cancer

Cell Mol Life Sci. 2019 Sep;76(17):3383-3406. doi: 10.1007/s00018-019-03134-0. Epub 2019 May 13.

Abstract

Emergence of novel treatment modalities provides effective therapeutic options, apart from conventional cytotoxic chemotherapy, to fight against colorectal cancer. Unfortunately, drug resistance remains a huge challenge in clinics, leading to invariable occurrence of disease progression after treatment initiation. While novel drug development is unfavorable in terms of time frame and costs, drug repurposing is one of the promising strategies to combat resistance. This approach refers to the application of clinically available drugs to treat a different disease. With the well-established safety profile and optimal dosing of these approved drugs, their combination with current cancer therapy is suggested to provide an economical, safe and efficacious approach to overcome drug resistance and prolong patient survival. Here, we review both preclinical and clinical efficacy, as well as cellular mechanisms, of some extensively studied repurposed drugs, including non-steroidal anti-inflammatory drugs, statins, metformin, chloroquine, disulfiram, niclosamide, zoledronic acid and angiotensin receptor blockers. The three major treatment modalities in the management of colorectal cancer, namely classical cytotoxic chemotherapy, molecular targeted therapy and immunotherapy, are covered in this review.

Keywords: 5-Fluorouracil; Cetuximab; Immunotherapy; Irinotecan; Molecular targeted chemotherapy; Pembrolizumab.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antimetabolites / chemistry
  • Antimetabolites / pharmacology
  • Antimetabolites / therapeutic use
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Drug Repositioning*
  • Drug Resistance, Neoplasm* / drug effects
  • Humans
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Topoisomerase I Inhibitors / chemistry
  • Topoisomerase I Inhibitors / pharmacology
  • Topoisomerase I Inhibitors / therapeutic use

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antimetabolites
  • Antineoplastic Agents
  • Antineoplastic Agents, Immunological
  • Protein Kinase Inhibitors
  • Topoisomerase I Inhibitors